Transanal total mesorectal excision for rectal cancer has been suspended in Norway.

BACKGROUND: Transanal total mesorectal excision (TaTME) for rectal cancer has emerged as an alternative to the traditional abdominal approach. However, concerns have been raised about local recurrence. The aim of this study was to evaluate local recurrence after TaTME. Secondary aims included postoperative mortality, anastomotic leak and stoma rates. METHODS: Data on all patients who underwent TaTME were recorded and compared with those from national cohorts in the Norwegian Colorectal Cancer Registry (NCCR) and the Norwegian Registry for Gastrointestinal Surgery (NoRGast). Kaplan-Meier estimates were used to compare local recurrence. RESULTS: In Norway, 157 patients underwent TaTME for rectal cancer between October 2014 and October 2018. Three of seven hospitals abandoned TaTME after a total of five procedures. The local recurrence rate was 12 of 157 (7·6 per cent); eight local recurrences were multifocal or extensive. The estimated local recurrence rate at 2·4 years was 11·6 (95 per cent c.i. 6·6 to 19·9) per cent after TaTME compared with 2·4 (1·4 to 4·3) per cent in the NCCR (P < 0·001). The adjusted hazard ratio was 6·71 (95 per cent c.i. 2·94 to 15·32). Anastomotic leaks resulting in reoperation occurred in 8·4 per cent of patients in the TaTME cohort compared with 4·5 per cent in NoRGast (P = 0·047). Fifty-six patients (35·7 per cent) had a stoma at latest follow-up; 39 (24·8 per cent) were permanent. CONCLUSION: Anastomotic leak rates after TaTME were higher than national rates; local recurrence rates and growth patterns were unfavourable.

ANTECEDENTES: La resección total del mesorrecto transanal (transanal total mesorectal excision, TaTME) para el cáncer de recto se ha propuesto como una alternativa al abordaje abdominal tradicional. Sin embargo, la recidiva local (local recurrence, LR) después de este procedimiento es motivo de preocupación. El objetivo de este estudio fue evaluar la LR en pacientes operados mediante TaTME. Los objetivos secundarios incluyeron la mortalidad postoperatoria, las fugas anastomóticas y el porcentaje de estomas. MÉTODOS: Se registraron los datos de todos los pacientes operados mediante TaTME y se compararon con las cohortes nacionales del Registro Noruego de Cáncer Colorrectal (Norwegian Colorectal Cancer Registry, NCCR) y del Registro Noruego de Cirugía Gastrointestinal (Norwegian Registry for Gastrointestinal Surgery, NoRGast) utilizando estimaciones de Kaplan-Meier y la prueba de log-rank para comparar curvas de LR. RESULTADOS: En Noruega, 157 pacientes se sometieron a TaTME por cáncer de recto entre octubre de 2014 y octubre de 2018. Tres de siete hospitales abandonaron el TaTME después de un total de cinco procedimientos. La LR observada fue 12/157 (7,6%), siendo ocho de ellas multifocales o extensas. La tasa estimada de LR a 2,4 años fue de 11,6 % (i.c. del 95% 6,6 a 19,9) versus 2,4 % (1,4 a 4,3) en el NCCR (log rank P < 0,001). El cociente de riesgos instantáneos (hazard ratio, HR) ajustado fue 6,7 (i.c. del 95% 2,9 a 15,3). Las fugas anastomóticas que precisaron una reintervención después de TaTME ocurrieron en un 8,4% versus 4,5% en el registro NoRGast (P = 0,047). Cincuenta y seis pacientes (35,7%) tenían un estoma en el último seguimiento; 39 (24,8%) eran permanentes. CONCLUSIÓN: Las tasas de fuga anastomótica tras una TaTME fueron más altas que los datos nacionales con tasas de LR y patrones de crecimiento desfavorables.

Prognostic impact of genomic instability in colorectal cancer.

BACKGROUND: The prognostic impact of an indication of chromosomal instability (CIN) is evaluated in a consecutive series of 952 colorectal cancer patients treated at Aker University Hospital, Norway, during 1993-2003. Microsatellite instability (MSI) in this case series has recently been reported and made it possible to find the co-occurrence and compare the prognostic significance of CIN and MSI. METHODS: Data sets for overall survival (OS; n=855) and time to recurrence (TTR; n=579) were studied. To reveal CIN we used automated image cytometry (ICM). Non-diploid histograms were taken as indicative of the presence of CIN. PCR-based measures of MSI in this material have already been described. RESULTS: As with MSI, CIN was found to be an independent predictor of early relapse and death among stage II patients (TTR: n=278: HR 2.19 (95% CI: 1.35-3.55), P=0.002). Of the MSI tumours (16%), 71% were found to be DNA diploid, 21% were DNA tetraploid and 8% were DNA aneuploid. Among microsatellite stable tumours, 24% were DNA diploid, 15% were DNA tetraploid and 61% were DNA aneuploid. CONCLUSION: For patients presenting with stage II disease, genomic instability as detected by DNA image cytometry has the potential to provide a useful biomarker for relapse and cancer-related death following surgery with curative intent.

Microsatellite instability has a positive prognostic impact on stage II colorectal cancer after complete resection: results from a large, consecutive Norwegian series.

BACKGROUND: Microsatellite instability (MSI) was suggested as a marker for good prognosis in colorectal cancer in 1993 and a systematic review from 2005 and a meta-analysis from 2010 support the initial observation. We here assess the prognostic impact and prevalence of MSI in different stages in a consecutive, population-based series from a single hospital in Oslo, Norway. PATIENTS AND METHODS: Of 1274 patients, 952 underwent major resection of which 805 were included in analyses of MSI prevalence and 613 with complete resection in analyses of outcome. Formalin-fixed tumor tissue was used for PCR-based MSI analyses. RESULTS: The overall prevalence of MSI was 14%, highest in females (19%) and in proximal colon cancer (29%). Five-year relapse-free survival (5-year RFS) was 67% and 55% (P = 0.030) in patients with MSI and MSS tumors, respectively, with the hazard ratio (HR) equal to 1.60 (P = 0.045) in multivariate analysis. The improved outcome was confined to stage II patients who had 5-year RFS of 74% and 56% respectively (P = 0.010), HR = 2.02 (P = 0.040). Examination of 12 or more lymph nodes was significantly associated with proximal tumor location (P < 0.001). CONCLUSIONS: MSI has an independent positive prognostic impact on stage II colorectal cancer patients after complete resection.

Short term outcome after emergency and elective surgery for colon cancer.

OBJECTIVE: Emergency presentation of colon cancer is common and associated with high mortality and morbidity following surgical treatment. The purpose of this study was to evaluate postoperative mortality and complications in a consecutive and population based series. METHOD: All patients with adenocarcinoma of the colon diagnosed between 1993 and 2007 were registered prospectively. Postoperative mortality and complication rates in elective and emergency patients were compared. Logistic regression analysis was used to identify independent risk factors for postoperative complications. RESULTS: In the study period 1129 patients were admitted, of whom 279 (25%) presented as an emergency. A total of 999 (89%) patients underwent surgical treatment; 924 patients (82%) had a major resection. The mortality rate was 3.5% after elective and 10% after emergency operation with resection (P < 0.01), and the complication rate was 24% and 38% (P < 0.01), respectively. In patients with left-sided obstruction, the mortality rate after Hartmann's procedure was 19% compared to 3% after resection with primary anastomosis (P < 0.01). Multivariate analyses demonstrated that emergency operation, increasing age, advanced tumour stage and ASA class IV were independent risk factors for postoperative mortality. CONCLUSION: Emergency operation for colon cancer was associated with high rates of complications and mortality, indicating that immediate surgery should be avoided if possible. Decompression of left sided obstruction with a stent seems promising, whereas no conclusion can be made with regard to optimal procedure if stent placement fails; in this study Hartmann's procedure was associated with high mortality and morbidity.

Tumour location is a prognostic factor for survival in colonic cancer patients.

OBJECTIVE: To evaluate survival and prognostic factors in a consecutive series of colon cancer patients from a defined city population in Norway. METHOD: All patients with adenocarcinoma of the colon diagnosed between 1993 and 2000 were registered prospectively. Five-year actuarial survival and 5-year relative survival rates were calculated. Cox regression analyses were used to study the effect of prognostic factors on survival. RESULTS: In the study period 627 patients were admitted. Overall 5-year relative survival was 50% in females and 52% in males. Five-year relative survival in 410 (65%) patients operated with curative intent, was 74% for females and 79% for males. Tumour location in the transverse colon, splenic flexure and descending colon (OR = 1.8), emergency operation (OR = 1.7), TNM stage (OR = 1.8-2.9), blood transfusion of more than two units (OR = 1.8) and age (OR = 4.0-7.1) were independent negative prognostic factors. CONCLUSION: Colon cancer located in the transverse and descending colon is associated with poor prognosis. Comparison of results from different centres is difficult due to selection and classification differences, and different methods used for calculation of survival.

Chemical composition, digestibility and emulsification properties of octenyl succinic esters of various starches.

Octenyl succinate starches are commonly used as emulsifiers and texturizing agents in many food-systems. Rice, tapioca, corn, wheat and potato starches were modified with octenyl succinic anhydride (OSA) at 3% level. Structural characterization, molecular weight, starch digestibility and physical properties of starch granule stabilized emulsions were studied for modified starches. Modified potato (0.022) and wheat (0.018) starches had the highest and lowest degrees of OSA substitution, respectively. For all starches, amylose and amylopectin molecular mass was significantly (P<0.05) lower for OSA starches. OSA modification may have hydrolyzed the small amylose and amylopectin chains, or caused rearrangement of the starch molecules. Although the starch modification improved emulsification properties, botanical source showed more influence on this parameter. Overall, botanical source had more influence on functional properties than degree of substitution. Further studies on OSA group distribution and fine molecular structure of amylopectin and relationship with functional properties will be important.

Deletion mapping of a retinal cone-rod dystrophy: assignment to 18q211.

Deletion of 18q211 was observed in a mentally retarded young man with electrophysiologically demonstrated cone-rod dystrophy, present since childhood. He had hypogonadism and a central postsynaptic hearing impairment. This is the first case of a chromosome deletion in a patient with a cone-rod dystrophy. Three patients with more distal deletions on chromosome 18 did not present retinal dystrophies. We suggest that one of the loci for cone-rod dystrophy may be located on chromosome 18 at q211-213. Reports of similar findings will be necessary for confirmation of this assumption.

Long-term botulinum toxin treatment of cervical dystonia--EMG changes in injected and noninjected muscles.

OBJECTIVE: To evaluate changes in quantitative EMG of injected and noninjected sternocleidomastoid muscles following long-term unilateral botulinum toxin treatment of cervical dystonia. METHODS: We investigated 27 patients with cervical dystonia, who received repeated unilateral botulinum toxin injections of the sternocleidomastoid muscle, with quantitative EMG at rest and at maximal voluntary contraction. The patients had on the average 7.1 botulinum toxin treatments and the follow-up period was on the average 31 months (SD 16). RESULTS: After the first treatment, the injected sternocleidomastoid muscles showed a significant decrease in turns/s (mean 45%) and amplitude (mean 52%) at rest, and in amplitude at maximal flexion (mean 24%) and rotation (mean 39%). Except for a reduction in turns/s at rotation (mean 19%) no further reductions in EMG parameters were seen after long-term treatment. The contralateral noninjected sternocleidomastoid muscles showed no significant change in EMG activity after the first BT treatment, but after long-term treatment a significant reduction in turns/s and amplitude at both maximal flexion (turns: mean 28%; amplitude: mean 25%) and rotation (turns/s: mean 32%; amplitude: mean 25%) were seen as compared to pretreatment values. CONCLUSION: The results indicate that there seems to be no cumulative chemodenervation by repeated botulinum toxin injections of sternocleidomastoid muscles measured by quantitative EMG. Contralateral noninjected sternocleidomastoid muscles however, seem to be affected following long-term treatment. The mechanism behind this finding is unknown.

Quantitative EMG in cervical dystonia.

Within the latest years botulinum toxin A (BT) applied locally in affected muscles has gained a superior position in the treatment of cervical dystonia. EMG is often used as a guidance for the injections, which has caused a need for better knowledge about the electromyographic changes in the muscles involved. In the present study we used the turns-amplitude analysis for the quantitative evaluation of the EMG of the sternocleidomastoid muscles and posterior neck muscles in 44 patients with cervical dystonia, not previously treated with BT. Twelve healthy subjects were examined for comparison. At rest 13 patients showed abnormal activity (defined as > 100 turns/s) in the sternocleidomastoid muscle contralateral to the involuntary head rotation (CS) and the ipsi- and contralateral posterior neck muscles (IPN and CPN): 12 patients had abnormal activity in CS and IPN, and seven patients had abnormal activity in all muscles, including the ipsilateral sternocleidomastoid muscle (IS). Other combinations were seen less often. The distribution of muscles with abnormal activity was not always obvious from the clinical examination. CPN and IS, i.e., apparently unaffected muscles, showed reduced EMG activity during attempted maximal voluntary contraction, indicating difficulties in activating all motor units.

Quantitative electromyographical changes in cervical dystonia after treatment with botulinum toxin.

Injection of botulinum toxin (BT) into affected neck muscles gives symptomatic relief to patients with cervical dystonia by causing a presynaptic block of acetylcholine release. In a retrospective study of 19 patients, we used the turns-amplitude analysis of the EMG interference pattern for the evaluation of electrophysiological changes as a function of time after BT treatment. EMG was performed immediately before and during injection, and muscles showing abnormally increased activity (> 100 turns/s at rest) were given botulinum toxin A (Oculinum (= Botox)) 40-120 units. A second EMG was done 6-30 weeks later. At attempted rest, the sternocleidomastoid muscle contralateral to the involuntary head rotation showed the most pronounced changes, possibly due to relatively large doses of BT, and the EMG changes were related to the time after BT treatment. Six weeks after treatment the muscle showed decreased turns/s, mean amplitude and ratio (turns/amplitude) at rest. At 30 weeks, turns and mean amplitude reached values as before treatment, while ratio was increased to 175% of the pre-treatment value. This pattern may reflect a reversible and random loss of muscles fibres, due to presynaptic denervation. At maximal voluntary contractions, no correlation was seen between time after BT treatment and quantitative EMG.

Mitochondrial myopathy as a cause of ptosis and ophthalmoplegia in elderly females.

Of 27 patients with ptosis and ophthalmoplegia or both, and abnormal mitochondria in proximal limb muscles, 13 were elderly females, in whom symptoms began late in life. Clinical, electrophysiological, and morphological findings are presented, and possible etiological factors are discussed. The ocular mitochondriopathy in post-menopausal females seems to represent a separate, previously not described syndrome.

Evoked potentials in multiple sclerosis before and after high-dose methylprednisolone infusion.

We studied 8 patients with definite multiple sclerosis (3 with acute relapse, 5 with progression), and 2 patients with acute optic neuritis, who were treated with methylprednisolone infusions, 1 g daily for 3 days. Visual, brain stem-auditory and somatosensory-evoked potentials were used to test the effect of therapy. There were no manifest changes of the evoked potentials parameters parallel to the clinical effect of high-dose therapy.

Retinal cone dysfunction and mental retardation associated with a de novo balanced translocation 1;6(q44;q27).

The authors describe a six-year-old boy with cone dystrophy, mental retardation, facial dysmorphism and short neck, hands and feet in whom they found a 1:6 chromosomal translocation. This is the first description of retinal cone dystrophy and a chromosomal aberration. The hypothesize that the cone dystrophy in the patient may be assigned to 1q44 or 6q27.

"Anticonvulsant action" of vitamin D in epileptic patients? A controlled pilot study.

The frequency of epileptic seizures was observed in a controlled therapeutic trial on 23 epileptic inpatients before and after treatment with vitamin D(2) or placebo in addition to anticonvulsant drugs. The number of seizures was reduced during treatment with vitamin D(2) but not with placebo. The effect was unrelated to changes in serum calcium or magnesium. The results may support the concept that epileptics should be treated prophylactically with vitamin D.

Acuity card testing of patients with cerebral visual impairment.

Acuity card tests of 11 patients with cerebral visual impairment, unexplained by clinical and electrophysiological ophthalmic examinations, confirmed the suspicion of severe visual impairment in all but one patient, but resulted in acuity estimates higher than previous evaluations for all nine of the patients for whom an estimate could be made. Relatively good inter-test agreement supports the use of acuity cards for the quantitative evaluation of the vision of these patients.

Duchenne muscular dystrophy: negative electroretinograms and normal dark adaptation. Reappraisal of assignment of X linked incomplete congenital stationary night blindness.

Aland Island eye disease (AIED) and X linked congenital stationary night blindness (CSNB) have been mapped to Xp11.3. Patients have been described with deletions of the Duchenne muscular dystrophy (DMD) gene who also had a negative electroretinogram (ERG) similar to that seen in patients with CSNB and AIED. This seems to confirm that some cases of AIED and CSNB map to Xp21. We examined 16 boys with DMD/BMD (Becker muscular dystrophy) of whom 10 had negative ERGs, eight of them having deletions downstream from exon 44. Normal dark adaptation thresholds were observed in all patients and there were no anomalous visual functions. Hence, CSNB cannot be assigned to Xp21 and negative ERG in DMD/BMD is not associated with eye disease. Six boys with DMD/BMD had normal ERGs. We speculate that a retinal or glial dystrophin may be truncated or absent in the boys with negative ERGs.

Ocular myopathy and mitochondrial DNA deletion. A presentation of seven identified Danish patients.

This paper summarizes the data on Danish patients with ocular myopathy and mitochondrial DNA deletion (delta mtDNA). To date, a single Danish patient harbouring delta mtDNA has been reported. In the present study we have identified seven additional ones and characterized the nature of their deletion, both qualitatively and quantitatively. All patients are sporadic cases each with a single deletion in the range of 2.3-78 kb, the delta mtDNA accounting for 10-75% of the total mtDNA in the biopsy analyzed. The clinical severity correlates with the percentage of deletion molecules, and not with the size of the deletion.

Saturable metabolic pathways for ethotoin in man.

1. The urinary excretion pattern of ethotoin and five metabolites were examined in three patients receiving continuous treatment with ethotoin at two dose levels, in order to investigate the mechanism behind the dose-dependent kinetics of this anticonvulsant drug. 2. The results suggest a partial saturation in the dealkylation process at high dose levels in three patients. 3. A rough approximation of the Michaelis-Menten constants for different enzymatic processes was attempted. On the basis of the results obtained, the p-hydroxylation may be a saturable process. 4. The dose-dependent kinetics of ethotoin in man seem to be explicable by the existence of partly saturable enzymatic pathways.

Pharmacokinetics and side-effects of clonazepam and its 7-amino-metabolite in man.

Clonazepam (CNP) and its principal metabolite in plasma, 7-amino-CNP (ACNP), have been investigated in a prospective study of 27 newly diagnosed epileptics and correlated with specified side-effects. At a daily dose of 6 mg, the average plasma levels of both substances were about 50ng/ml, and individual values ranged from 30 to about 80 ng/ml. There was a linear correlation between changes in dose and the resulting plasma levels, which indicates first order elimination kinetics. Side-effects were frequent, but neither their severity nor their occurrence could be related to plasma levels or to the rate of increase in plasma concentration of the drug. Three out of five patients who developed serious dysphoria had significantly high CNP levels. The concentration of ACNP was considerably increased in four patients who subsequently suffered from withdrawal symptoms. Drug interaction with diphenylhydantoin, i.e. decreased CNP level, was observed in all five patients who received both compounds. In general it is not yet possible to define an upper limit for the plasma levels of CNP and ACNP at which toxicity occurs. In patients treated with conventional doses of CNP, measurement of plasma concentration is not required, except in special circumstances, because of the lack of correlation between plasma level and side-effects.